Adenovirus-mediated expression of spermidine/spermine N1-acetyltransferase gene induces S-phase arrest in human colorectal cancer cells.
Spermidine/spermine N1-acetyltransferase (SSAT) is a key enzyme of polyamine catabolism. In a previous study, we constructed a recombinant adenovirus, Ad-SSAT, which can express human SSAT. In the present study, we investigated the effect of Ad-SSAT on the growth and cell cycle of colorectal cancer cells. We found that Ad-SSAT increased the expression of SSAT and inhibited the growth of HT-29 and Lovo cells. The growth inhibition was caused by cell cycle arrest in the S phase. Furthermore, Ad-SSAT was shown to suppress the expression of cyclin A and nuclear factor E2F-1 in HT-29 and Lovo cells. The inhibitory effect of Ad-SSAT on cyclin A promoter activity was also observed in a reporter gene assay. Our results suggest that the expression of SSAT mediated by Ad-SSAT infection inhibits the growth of colorectal cancer cells and induces cell cycle arrest at the S phase, through a mechanism involving the suppression of cyclin A and E2F-1 expression.
Sun
Hui
H
Institute of Biochemistry and Molecular Biology, School of Medicine, Shandong University, Jinan, P.R. China.
Liu
Bin
B
Wang
Wei
W
Jiang
Guang-Shui
GS
Li
Wei
W
Yang
Ya-Pei
YP
Xu
Chun-Xiao
CX
Yan
Yun-Fei
YF
Liu
Xian-Xi
XX
D000123:Acetyltransferases / Q000235:genetics* / Q000378:metabolism; D000256:Adenoviridae / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000502:physiology*; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013095:Spermidine / Q000502:physiology*; D014162:Transfection; D000099228:Diamine N-Acetyltransferase
D000123:Acetyltransferases; D019925:Cyclin A; D050687:E2F1 Transcription Factor; D013095:Spermidine; D000099228:Diamine N-Acetyltransferase